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Background: Tofacitinib is an oral JAK inhibitor for the treatment of ulcerative colitis (UC). We assessed outcomes through 78 weeks of tofacitinib therapy for UC in a real-world setting., Methods: This retrospective cohort study included adults initiating tofacitinib for UC from May 1, 2018, to April 1, 2021, at a large academic center in the United States. The primary outcome was steroid-free clinical remission at 78 (+/-4) weeks (SFCR 78; simple clinical colitis activity index ≤2 with no corticosteroid use within 30 days). The secondary outcome was tofacitinib discontinuation due to nonresponse (treatment persistence). Additional outcomes were endoscopic response/remission and adverse events (AEs)., Results: Seventy-three patients initiated tofacitinib, with a median follow-up of 88 weeks. Among patients with available data, 31 of 60 (51.7%) achieved SFCR 78, 21 of 47 (44.7%) achieved endoscopic remission during follow-up, and 25 of 73 (34.2%) discontinued tofacitinib during follow-up due to nonresponse (including 11 patients who required colectomy). Nineteen AEs were reported among 15 patients during follow-up: shingles (n = 4, all without documented vaccinations), deep venous thrombosis (n = 2), elevated liver enzymes (n = 2), skin abscess (n = 2), pneumonia (n = 2), possible miscarriage (n = 2), norovirus (n = 1), COVID-19 (n = 1), lymphopenia (n = 1), Clostridioides difficile infection (n = 1), and heart block (n = 1). One patient discontinued therapy due to an AE (elevated liver enzymes), and no deaths occurred., Conclusion: Tofacitinib treatment was effective in achieving SFCR for the majority of patients with UC through 78 weeks. Adverse events were consistent with the known safety profile of tofacitinib, and AEs requiring discontinuation were rare. Due to limitations regarding sample size, larger studies are needed to confirm these findings., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Patients with inflammatory bowel disease (IBD) develop coronavirus disease 2019 (COVID-19) at similar rates as the general population, and there was initial concern regarding potential for severe illness. 1-4 Vaccinations were authorized for emergency use in the United States in December 2020 and aim to halt the spread of COVID-19. However, there are concerns that people will be hesitant to receive the vaccine for a variety of reasons including insufficient data in certain populations including those with IBD. We surveyed patients with IBD to identify potential concerns regarding COVID-19 vaccination., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Fecal microbiota transplantation (FMT) is used commonly for treatment of Clostridioides difficile infections (CDIs), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers., Methods: Patients undergoing FMT in clinical practices across North America were eligible. Participating investigators enter de-identified data into an online platform, including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes., Results: Of the first 259 participants enrolled at 20 sites, 222 had completed short-term follow-up at 1 month and 123 had follow-up to 6 months; 171 (66%) were female. All FMTs were done for CDI and 249 (96%) used an unknown donor (eg, stool bank). One-month cure occurred in 200 patients (90%); of these, 197 (98%) received only 1 FMT. Among 112 patients with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (n = 5 [2%]) and abdominal pain (n = 4 [2%]); 3 patients (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%)., Conclusions: This prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT., (Copyright © 2021. Published by Elsevier Inc.)

A subset of patients with ulcerative colitis (UC) present with, or progress to, moderate to severe disease activity. These patients are at high risk for colectomy, hospitalization, corticosteroid dependence, and serious infections. The risk of life-threatening complications and emergency colectomy is particularly high among those patients hospitalized with acute severe ulcerative colitis. Optimal management of outpatients or inpatients with moderate to severe UC often requires the use of immunomodulator and/or biologic therapies, including thiopurines, methotrexate, cyclosporine, tacrolimus, TNF-α antagonists, vedolizumab, tofacitnib, or ustekinumab, either as monotherapy or in combination (with immunomodulators), to mitigate these risks. Decisions about optimal drug therapy in moderate to severe UC are complex, with limited guidance on comparative efficacy and safety of different treatments, leading to considerable practice variability. Therefore, the American Gastroenterological Association prioritized development of clinical guidelines on this topic. To inform the clinical guidelines, this technical review was completed in accordance with the Grading of Recommendations Assessment, Development and Evaluation framework. Focused questions in adult outpatients with moderate to severe UC included: (1) overall and comparative efficacy of different medications for induction and maintenance of remission in patients with or without prior exposure to TNF-α antagonists, (2) comparative efficacy and safety of biologic monotherapy vs combination therapy with immunomodulators, (3) comparative efficacy of top-down (upfront use of biologics and/or immunomodulator therapy) vs step-up therapy (acceleration to biologic and/or immunomodulator therapy only after failure of 5-aminosalicylates, and (4) role of continuing vs stopping 5-aminosalicylates in patients being treated with immunomodulator and/or biologic therapy for moderate to severe UC. Focused questions in adults hospitalized with acute severe ulcerative colitis included: (5) overall and comparative efficacy of pharmacologic interventions for inpatients refractory to corticosteroids, in reducing risk of colectomy, (6) optimal dosing regimens for intravenous corticosteroids and infliximab in these patients, and (7) role of adjunctive antibiotics in the absence of confirmed infections., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Clostridium difficile infection (CDI) has become the leading cause of nosocomial infection in the United States with significant risk of both morbidity and mortality. While antimicrobial therapy forms the basis of treatment, there are several clinical scenarios in which antimicrobial therapy alone is insufficient. Evidence continues to show the safety and efficacy fecal microbiota transplantation (FMT) in recurrent and severe CDI. This review will outline FMT efficacy, safety, and indications and present practical advice for clinicians interested in best practices around delivery of FMT., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)